The mitochondrial hinge protein, UQCRH, is a novel prognostic factor for hepatocellular carcinoma.

Abstract

Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-Meier analysis revealed significantly shorter overall (P = 0.005) and recurrence-free survival (P = 0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the α-fetoprotein (AFP) level. The patient subgroup with higher AFP levels (≥20 ng/mL) exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (<20 ng/mL). Multivariate analysis defined UQCRH as an independent poor prognostic factor. Conclusively, our results indicate that UQCRH overexpression is correlated with poor outcomes of HCC patients. Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH overexpression could be a useful indicator for clinical treatment.

• Authors: Eun-Ran Park, Sang-Bum Kim, Jee-San Lee, Yang-Hyun Kim, Dong-Hyoung Lee, Eung-Ho Cho, Sun-Hoo Park, Chul Ju Han, Bu-Yeo Kim, Dong Wook Choi, Young Do Yoo, Ami Yu, Jae Won Lee, Ja June Jang, Young Nyun Park, Kyung-Suk Suh, Kee-Ho Lee
• Journal: Cancer medicine (Cancer Med) Vol. 6 Issue 4 Pg. 749-760 (Apr 2017) ISSN: 2045-7634 [Electronic] United States
• PMID: 28332314 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Hepatitis B Surface Antigens
• UQCRH protein, human
• Electron Transport Complex III

Topics

• Adult
• Aged
• Carcinoma, Hepatocellular (genetics, immunology, pathology, virology)
• Electron Transport Complex III (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Hepatitis B (immunology)
• Hepatitis B Surface Antigens (metabolism)
• Humans
• Liver Neoplasms (genetics, immunology, pathology, virology)
• Male
• Middle Aged
• Prognosis
• Tumor Burden
• Up-Regulation